Cancer pathogenesis and therapy最新文献

英文中文

Factors affecting the place of death in patients with liver cancer in China, 2013–2020: A population-based study 2013-2020年影响中国肝癌患者死亡地点的因素：基于人口的研究

Cancer pathogenesis and therapy

Pub Date : 2024-04-01 DOI: 10.1016/j.cpt.2024.04.001

Xiaosheng Ding, Weiwei Shi, Jinlei Qi, Juan An, Weiran Xu, Hui Shi, Xixi Zheng, Xiaoyan Li

引用次数: 0

Association between autoimmunity-related disorders and prostate cancer: A Mendelian randomization study 自身免疫相关疾病与前列腺癌之间的关系：孟德尔随机研究

Cancer pathogenesis and therapy

Pub Date : 2024-03-29 DOI: 10.1016/j.cpt.2024.03.002

Background

Although many epidemiological studies and meta-analyses have reported an association between autoimmune disorders and prostate cancer, none has reported a clear correlation or the direction of the association. The purpose of our study was to explore the potential relationship between autoimmunity-related disorders and prostate cancer using Mendelian randomization (MR).

Methods

We retrieved literature from PubMed using the keywords “autoimmune disorder” AND “prostate cancer” to find more clues on the correlation between prostate cancer and autoimmunity-related disorder. Based on this literature search, we selected 16 autoimmunity-related disorders that had genome-wide association study (GWAS) data and may be associated with prostate cancer. The inverse variance weighting (IVW) method was applied as our primary analysis for two-sample MR and multivariate MR analysis to estimate the odds ratio (OR) and 95% confidence interval (CI). We further verified the robustness of our conclusions using a series of sensitivity analyses.

Results

The autoimmunity-related diseases selected include rheumatoid arthritis, ankylosing spondylitis, coxarthrosis, gonarthrosis, Crohn's disease, ulcerative colitis, irritable bowel syndrome, celiac disease, primary sclerosing cholangitis, asthma, type 1 diabetes, systemic lupus erythematosus, multiple sclerosis, autoimmune hyperthyroidism, psoriatic arthropathies, and polymyalgia rheumatica. The results of inverse variance weighting (IVW suggested that six diseases were associated with the development of prostate cancer. The three diseases that may increase the risk of prostate cancer are rheumatoid arthritis (P = 0.001), coxarthrosis (P < 0.001), and gonarthrosis (P = 0.008). The three possible protective factors against prostate cancer are primary sclerosing cholangitis (P = 0.001), autoimmune hyperthyroidism (P = 0.011), and psoriatic arthropathies (P = 0.001). Horizontal pleiotropy was not observed in the MR-Egger test.

Conclusions

Our findings provide predictive genetic evidence for an association between autoimmune disorders and prostate cancer. Further research is needed to explore the underlying mechanisms of comorbidities at the molecular level.

背景尽管许多流行病学研究和荟萃分析报告了自身免疫性疾病与前列腺癌之间的关系，但没有一项研究报告了两者之间的明确相关性或关系的方向。我们使用关键词 "自身免疫性疾病 "和 "前列腺癌 "在PubMed上检索文献，以寻找更多有关前列腺癌与自身免疫性疾病相关的线索。在文献检索的基础上，我们选择了16种有全基因组关联研究（GWAS）数据且可能与前列腺癌相关的自身免疫相关疾病。我们采用反方差加权法（IVW）作为主要分析方法，进行双样本 MR 分析和多变量 MR 分析，以估算几率比（OR）和 95% 置信区间（CI）。我们通过一系列敏感性分析进一步验证了结论的稳健性。结果所选的自身免疫相关疾病包括类风湿性关节炎、强直性脊柱炎、髋关节病、寰枢关节病、克罗恩病、溃疡性结肠炎、肠易激综合征、乳糜泻、原发性硬化性胆管炎、哮喘、1 型糖尿病、系统性红斑狼疮、多发性硬化症、自身免疫性甲状腺功能亢进症、银屑病关节病和多发性风湿痛。逆方差加权（IVW）的结果表明，有六种疾病与前列腺癌的发病有关。可能增加前列腺癌风险的三种疾病是类风湿性关节炎（P = 0.001）、髋关节病（P < 0.001）和膝关节病（P = 0.008）。原发性硬化性胆管炎（P = 0.001）、自身免疫性甲状腺功能亢进症（P = 0.011）和银屑病关节病（P = 0.001）可能是前列腺癌的三个保护因素。我们的研究结果为自身免疫性疾病与前列腺癌之间的关联提供了预测性遗传证据。我们的研究结果为自身免疫性疾病与前列腺癌之间的关联提供了预测性遗传证据。

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引用次数: 0

Cover 封面

Cancer pathogenesis and therapy

Pub Date : 2024-03-26 DOI: 10.1016/S2949-7132(24)00006-5

引用次数: 0

Long-term adoptive immunotherapy achieves complete response and bone lesion repair in an elderly patient with macrofocal multiple myeloma 长期采用免疫疗法使一名老年大灶多发性骨髓瘤患者获得完全应答并修复骨病变

Cancer pathogenesis and therapy

Pub Date : 2024-03-16 DOI: 10.1016/j.cpt.2024.03.001

引用次数: 0

Efficacy and safety of anlotinib plus penpulimab as second-line treatment for small cell lung cancer: A multicenter, open-label, single-arm phase II trial 安罗替尼加培罗单抗作为小细胞肺癌二线治疗的有效性和安全性：多中心、开放标签、单臂II期试验

Cancer pathogenesis and therapy

Pub Date : 2024-02-07 DOI: 10.1016/j.cpt.2024.02.001

Background

Currently, the need for new therapeutic strategies involving programmed cell death protein-1 (PD-1) monoclonal antibodies in the second-line setting of small cell lung cancer (SCLC) is urgent. This study aimed to evaluate the efficacy and safety of anlotinib plus penpulimab as a second-line treatment for patients with SCLC who progressed after first-line platinum-based chemotherapy.

Methods

This study included the patients from Cohort 4 of a single-arm, open-label, multicenter, phase II clinical trial. A safety run-in phase was performed under anlotinib (10/12 mg quaque die [QD], days 1–14) plus penpulimab (200 mg intravenously [IV], day 1) in a 21-day cycle, followed by the formal trial in which the patients received anlotinib (12 mg QD, days 1–14) plus penpulimab (200 mg IV, day 1) in a 21-day cycle. The primary endpoint of the safety run-in phase was safety. The primary endpoint of the formal trial phase was the objective response rate (ORR).

Results

From April 28, 2020, to November 24, 2020, 21 patients were enrolled from 11 hospitals, including 2 in the safety run-in phase and 19 in the formal trial phase. In the formal trial phase, the ORR was 42.1% (8/19; 95% confidence interval [CI]: 17.7–66.6%). The median progression-free survival was 4.8 months (95% CI: 2.9–11.3 months), and the median overall survival was 13.0 months (95% CI: 4.6–not applicable [NA] months). The incidence of ≥grade 3 treatment-related adverse events (TRAEs) was 52.4% (11/21), and the incidence of treatment-related serious adverse events (AEs) was 28.6% (6/21). Two AE-related deaths occurred. The most common AEs were hypertension (57.1%, 12/21), hypothyroidism (42.9%, 9/21), and hypertriglyceridemia (38.1%, 8/21).

Conclusions

In patients with SCLC who progressed after first-line platinum-based chemotherapy, the second-line anlotinib plus penpulimab treatment demonstrates promising anti-cancer activity and a manageable safety profile, which warrants further investigation.

Trial registration

No. NCT04203719, https://clinicaltrials.gov/.

背景目前，小细胞肺癌（SCLC）二线治疗急需使用程序性细胞死亡蛋白-1（PD-1）单克隆抗体的新治疗策略。本研究旨在评估安罗替尼联合戊普利单抗作为一线铂类化疗后病情进展的SCLC患者二线治疗的有效性和安全性。在安罗替尼（10/12 毫克，第 1-14 天，quaque die [QD]）+ Penpulimab（200 毫克，第 1 天，静脉注射[IV]）的 21 天周期内，患者接受安罗替尼（12 毫克，第 1-14 天，quaque die [QD]）+ Penpulimab（200 毫克，第 1 天，静脉注射[IV]）的 21 天周期治疗。安全运行阶段的主要终点是安全性。结果从2020年4月28日到2020年11月24日，共有来自11家医院的21名患者入组，其中安全运行阶段2人，正式试验阶段19人。在正式试验阶段，ORR 为 42.1%（8/19；95% 置信区间 [CI]：17.7-66.6%）。中位无进展生存期为4.8个月（95% CI：2.9-11.3个月），中位总生存期为13.0个月（95% CI：4.6-不适用[NA]个月）。≥3级治疗相关不良事件（TRAEs）发生率为52.4%（11/21），治疗相关严重不良事件（AEs）发生率为28.6%（6/21）。有两例与不良反应相关的死亡病例。最常见的不良反应是高血压（57.1%，12/21）、甲状腺功能减退（42.9%，9/21）和高甘油三酯血症（38.1%，8/21）。结论在一线铂类化疗后病情进展的SCLC患者中，二线安罗替尼加培罗单抗治疗显示出良好的抗癌活性和可控的安全性，值得进一步研究。试验登记号：NCT04203719，https://clinicaltrials.gov/。

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引用次数: 0

Self-healing hydrogels for enhancing chemotherapy drug efficacy: Advancements in anti-sarcoma and carcinoma therapies and clinical trial feasibility 用于提高化疗药物疗效的自愈合水凝胶：抗肉瘤和癌症疗法的进展与临床试验的可行性

Cancer pathogenesis and therapy

Pub Date : 2024-02-02 DOI: 10.1016/j.cpt.2024.01.003

Luc Taylor

引用次数: 0

Autophagy as a targeted therapeutic approach for skin cancer: Evaluating natural and synthetic molecular interventions 自噬作为皮肤癌的靶向治疗方法：评估天然和合成分子干预措施

Cancer pathogenesis and therapy

Pub Date : 2024-02-01 DOI: 10.1016/j.cpt.2024.01.002

Md. Liakot Ali , Amdad Hossain Roky , S.M. Asadul Karim Azad , Abdul Halim Shaikat , Jannatul Naima Meem , Emtiajul Hoque , Abu Mohammed Fuad Ahasan , Mohammed Murshedul Islam , Md. Saifur Rahaman Arif , Md. Saqline Mostaq , Md. Zihad Mahmud , Mohammad Nurul Amin , Md. Ashiq Mahmud

Skin cancer, a prevalent malignancy worldwide, poses significant health concerns owing to its increasing incidence. Autophagy, a natural cellular process, is a pivotal event in skin cancer and has advantageous and detrimental effects. This duality has prompted extensive investigations into medical interventions targeting autophagy modulation for their substantial therapeutic potential. This systematic review aimed to investigate the relationship between skin cancer and autophagy and the contribution and mechanism of autophagy modulators in skin cancer. We outlined the effectiveness and safety of targeting autophagy as a promising therapeutic strategy for the treatment of skin cancer. This comprehensive review identified a diverse array of autophagy modulators with promising potential for the treatment of skin cancer. Each of these compounds demonstrates efficacy through distinct physiological mechanisms that have been elucidated in detail. Interestingly, findings from a literature search indicated that none of the natural, synthetic, or semisynthetic compounds exhibited notable adverse effects in either human or animal models. Consequently, this review offers novel mechanistic and therapeutic perspectives on the targeted modulation of autophagy in skin cancer.

皮肤癌是一种全球流行的恶性肿瘤，由于其发病率不断上升，对人们的健康造成了极大的威胁。自噬是一种自然的细胞过程，在皮肤癌中起着关键作用，有利有弊。这种双重性促使人们广泛研究针对自噬调节的医疗干预措施，以挖掘其巨大的治疗潜力。本系统综述旨在研究皮肤癌与自噬之间的关系，以及自噬调节剂在皮肤癌中的作用和机制。我们概述了以自噬为靶点作为皮肤癌治疗策略的有效性和安全性。这篇综合综述发现了一系列具有治疗皮肤癌潜力的自噬调节剂。这些化合物中的每一种都通过已详细阐明的不同生理机制显示出疗效。有趣的是，文献检索结果表明，这些天然、合成或半合成化合物均未在人体或动物模型中表现出明显的不良反应。因此，本综述为有针对性地调节皮肤癌自噬提供了新的机制和治疗视角。

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引用次数: 0

Inetetamab combined with pyrotinib and oral vinorelbine for patients with human epidermal growth factor receptor 2 positive advanced breast cancer: A single-arm phase 2 clinical trial 伊奈他单抗联合吡罗替尼和口服长春瑞滨治疗人类表皮生长因子受体 2 阳性晚期乳腺癌患者：单臂 2 期临床试验

Cancer pathogenesis and therapy

Pub Date : 2024-01-01 DOI: 10.1016/j.cpt.2023.10.004

Nan Jin , Yi Xu , Siqi Wang , Chunxiao Sun , Xueqi Yan , Fan Yang , Yan Liang , Weiwei Chen , Xiang Huang

Background

Human epidermal growth factor receptor 2 (HER2)-targeted agents have significantly improved the outcomes of patients with HER2-positive breast cancer; however, a large proportion of patients still develop resistance to trastuzumab. In this study, we investigated the efficacy and safety of inetetamab, another anti-HER2 antibody, combined with pyrotinib and oral vinorelbine in patients with HER2-positive advanced breast cancer so as to provide new ideas for the treatment.

Methods

In this prospective, single-arm, phase 2 trial, patients with HER2-positive advanced breast cancer with disease progression after trastuzumab were recruited. Patients received a combination of inetetamab (loading dose of 8 mg/kg and subsequent doses of 6 mg/kg intravenously once every 3 weeks), pyrotinib (400 mg orally once daily), and vinorelbine (60 mg/m² orally once weekly) until disease progression or intolerable toxicity. The primary endpoint was progression-free survival (PFS). The secondary endpoints included objective response rate (ORR), overall survival (OS), disease control rate (DCR), and safety.

Results

Between February 13, 2022 and December 25, 2022, 30 patients were screened and enrolled in this study. The median age of the patients at enrollment was 54 years, 12 patients (40.0 %) had hormone-receptor-positive disease and 23 patients (76.7 %) had visceral metastasis. The median PFS was 8.63 months (95 % confidence interval [CI] 4.15–13.12 months). The median OS was not reached. The ORR was 53.3 % (16/30) and the DCR was 96.7 % (29/30). The most common Grade III/IV adverse events were leukopenia (n = 5, 16.7 %), neutropenia (n = 4, 13.3 %), and diarrhea (n = 3, 10 %). No treatment-related serious adverse events or deaths occurred.

Conclusions

The combination regimen of inetetamab, pyrotinib, and oral vinorelbine showed encouraging efficacy and favorable safety in patients with HER2-positive advanced breast cancer and could be considered as an alternative treatment option for the patients.

Trial registration

No.NCT05823623; https://www.clinicaltrials.gov/.

背景人类表皮生长因子受体2（HER2）靶向药物已显著改善了HER2阳性乳腺癌患者的预后；然而，仍有很大一部分患者对曲妥珠单抗产生了耐药性。本研究探讨了伊奈他单抗（另一种抗HER2抗体）联合吡罗替尼和口服长春瑞滨治疗HER2阳性晚期乳腺癌患者的疗效和安全性，以期为治疗提供新思路。方法在这项前瞻性、单臂、2期试验中，招募了曲妥珠单抗治疗后疾病进展的HER2阳性晚期乳腺癌患者。患者接受伊奈他单抗（负荷剂量为8毫克/千克，随后每3周静脉注射一次，剂量为6毫克/千克）、吡罗替尼（400毫克，口服，每天一次）和长春瑞滨（60毫克/平方米，口服，每周一次）的联合治疗，直至疾病进展或出现不可耐受的毒性反应。主要终点是无进展生存期（PFS）。次要终点包括客观反应率（ORR）、总生存率（OS）、疾病控制率（DCR）和安全性。结果2022年2月13日至2022年12月25日期间，本研究共筛选并招募了30名患者。入组患者的中位年龄为54岁，12名患者（40.0%）激素受体阳性，23名患者（76.7%）有内脏转移。中位生存期为8.63个月（95%置信区间[CI] 4.15-13.12个月）。未达到中位OS。ORR为53.3%（16/30），DCR为96.7%（29/30）。最常见的III/IV级不良事件为白细胞减少（5例，16.7%）、中性粒细胞减少（4例，13.3%）和腹泻（3例，10%）。结论伊奈他单抗、吡罗替尼和口服长春瑞滨的联合治疗方案在HER2阳性晚期乳腺癌患者中显示出令人鼓舞的疗效和良好的安全性，可作为患者的另一种治疗选择。试验登记号：NCT05823623；https://www.clinicaltrials.gov/。

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引用次数: 0

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Cancer pathogenesis and therapy

Pub Date : 2024-01-01 DOI: 10.1016/S2949-7132(23)00099-X

引用次数: 0

Bone metastasis is a late-onset and unfavorable event in survivors of gastric cancer after radical gastrectomy: Results from a clinical observational cohort 在胃癌根治术后的幸存者中，骨转移是一种晚发且不利的疾病：临床观察队列的结果

Cancer pathogenesis and therapy

Pub Date : 2024-01-01 DOI: 10.1016/j.cpt.2023.11.003

Cheng Zhang , Xiaopeng Zhang , Chong Feng , Yahui Yang , Minmin Xie , Ying Feng , Zhijun Wu , Hui Xu , Changhao Wu , Tai Ma

Background

The timing and incidence of recurrent bone metastasis (BM) after radical gastrectomy in patients with gastric cancer (GC) as well as the survival of these patients were not fully understood. The aim of this study was to analyze the data of an observational GC cohort and identify patients who underwent curative gastrectomy and had recurrent BM to describe and clarify the pattern and profile of BM evolution after surgery.

Methods

Data were retrieved from a hospital-based GC cohort, and patients who underwent upfront radical gastrectomy were selected. The time points of specific organ metastatic events were recorded, and the person-year incidence rate of metastatic events was calculated. The latency period of BM events after gastrectomy was measured and compared with that of the other two most common metastatic events, liver metastasis (LM) and distant lymph node metastasis (LNM), using analysis of variance. Propensity score matching and subgroup analysis were used for sensitivity analysis.

Results

A total of 1324 GC cases underwent radical gastrectomy between January 2011 and December 2021. Of these, 67 BM, 218 LM, and 248 LNM occurred before the last follow-up. The incidence of BM events was 1.7/100 person-years, which was approximately 3-fold lower than that of LM and distant LNM events (5.5 and 6.3 per 100 person-years, respectively). BM events had a significantly longer latency (median time, 16.5 months) than LM and LNM events (11.1 and 12.0 months, respectively). Recurrent BM led to a worse prognosis (median survival, 4.5 months) than those of LM and LNM events (median survival, 7.7 and 7.1 months, respectively). However, no difference in overall survival after gastrectomy was observed among the groups.

Conclusions

Compared with other common metastatic events, BM in GC after gastrectomy is a late-onset event indicating poor survival.

Trial registration

No. ChiCTR1800019978; http://www.chictr.org.cn/.

背景胃癌（GC）根治性胃切除术后复发骨转移（BM）的时间和发生率以及这些患者的生存率尚不完全清楚。本研究的目的是分析观察性胃癌队列的数据，找出接受根治性胃切除术后出现复发性骨转移的患者，以描述和阐明术后骨转移演变的模式和概况。记录特定器官转移事件的时间点，并计算转移事件的人年发生率。采用方差分析法测量了胃切除术后BM事件的潜伏期，并与其他两种最常见的转移事件（肝转移（LM）和远处淋巴结转移（LNM））的潜伏期进行了比较。结果 2011年1月至2021年12月期间，共有1324例GC病例接受了根治性胃切除术。其中，67 例 BM、218 例 LM 和 248 例 LNM 发生在最后一次随访之前。BM事件的发生率为1.7/100人年，比LM和远处LNM事件的发生率（分别为5.5/100人年和6.3/100人年）低约3倍。BM事件的潜伏期（中位时间，16.5个月）明显长于LM和LNM事件（分别为11.1个月和12.0个月）。与 LM 和 LNM（中位生存期分别为 7.7 个月和 7.1 个月）相比，复发 BM 的预后更差（中位生存期为 4.5 个月）。结论与其他常见转移事件相比，胃切除术后GC的BM是一种晚发事件，预示着生存率较低。试验登记号：ChiCTR1800019978；http://www.chictr.org.cn/。

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